92-95-5Relevant articles and documents
Staphylococcus aureus rnpa inhibitors: Computational-guided design, synthesis and initial biological evaluation
Suigo, Lorenzo,Chojnacki, Michaelle,Zanotto, Carlo,Sebastián-Pérez, Victor,Morghen, Carlo De Giuli,Casiraghi, Andrea,Dunman, Paul M.,Valoti, Ermanno,Straniero, Valentina
, (2021/05/04)
Antibiotic resistance is spreading worldwide and it has become one of the most important issues in modern medicine. In this context, the bacterial RNA degradation and processing machinery are essential processes for bacterial viability that may be exploited for antimicrobial therapy. In Staphylococcus aureus, RnpA has been hypothesized to be one of the main players in these mech-anisms. S. aureus RnpA is able to modulate mRNA degradation and complex with a ribozyme (rnpB), facilitating ptRNA maturation. Corresponding small molecule screening campaigns have recently identified a few classes of RnpA inhibitors, and their structure activity relationship (SAR) has only been partially explored. Accordingly, in the present work, using computational modeling of S. aureus RnpA we identified putative crucial interactions of known RnpA inhibitors, and we used this information to design, synthesize, and biologically assess new potential RnpA inhibitors. The present results may be beneficial for the overall knowledge about RnpA inhibitors belonging to both RNPA2000-like thiosemicarbazides and JC-like piperidine carboxamides molecular classes. We evaluated the importance of the different key moieties, such as the dichlorophenyl and the piperidine of JC2, and the semithiocarbazide, the furan, and the i-propylphenyl ring of RNPA2000. Our efforts could provide a foundation for further computational-guided investigations.
Development of synthetic aminopeptidase N/CD13 inhibitors to overcome cancer metastasis and angiogenesis
Su, Li,Cao, Jiangying,Jia, Yuping,Zhang, Xiaonan,Fang, Hao,Xu, Wenfang
supporting information, p. 959 - 964 (2013/02/23)
Cancer metastasis is a major barrier to its treatment and an important cause of patient death. Antimetastatic agents hold promise for patients with advanced metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an important target against cancer metastasis and angiogenesis, but there are few reports on the in vivo evaluation of synthetic APN inhibitors. Herein, a series of compounds targeting APN were synthesized and evaluated for their antimetastasis and antiangiogenesis potency both in vitro and in vivo. Excitingly, compounds 4m, 4t, and 4cc, with the most potent APN inhibitory activities, displayed significant antimetastasis and antiangiogenesis effects in vitro and in vivo, suggesting that those synthetic APN inhibitors have the potential to overcome cancer metastasis and angiogenesis.
Antitumor activity of 3,4-dihydroquinazoline dihydrochloride in A549 xenograft nude mice
Jung, Soo Yeon,Lee, So Hyung,Kang, Han Byul,Park, Hang Ah,Chang, Sun Ki,Kim, Jungahn,Choo, Dong Joon,Oh, Chun Rim,Kim, Young Deuk,Seo, Ji Hyung,Lee, Kyung-Tae,Lee, Jae Yeol
experimental part, p. 6633 - 6636 (2010/12/19)
In the previous article we have reported that 3,4-dihydroquinazoline 1 is a potent and selective T-type calcium channel blocker that exhibited strong anti-cancer activity in vitro. Compound 1·2HCl was further in vivo evaluated against A549 xenograft in BALB/c nude mice, which exhibited 49% tumor-weight inhibition through intravenous administration of 2 mg/kg of body weight and was more potent than doxorubicin. Moreover, compound 1·2HCl has an oral bioavailability of 98% with LD50 values of 693 mg/kg (po route) and 40.0 mg/kg (iv route) of body weight. In addition, its efficient scale-up synthetic method was developed.
